Epidermal Growth Factor Stimulates Human Trophoblast Cell Migration through Rho A and Rho C Activation
Epidermal Growth Factor Stimulates Human Trophoblast Cell Migration through Rho A and Rho C Activation
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表皮生长因子通过 Rho A 和 rho C 激活刺激人滋养层细胞迁移
DOI：
10.1210/en.2009-0845
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发表时间：
2010-04-01
期刊：
影响因子：
4.8
通讯作者：
Zhou, Yuanguo
中科院分区：
文献类型：
--
作者：
Han, Jian;Li, Li;Zhou, Yuanguo
本研究探讨Rho蛋白在表皮生长因子（EGF）诱导的滋养层细胞迁移中的作用及其机制。使用绒毛膜癌细胞系JEG-3和ESTA和第一个三个月的人绒毛膜绒毛外植体培养基质胶，我们研究了EGF介导的刺激滋养层细胞迁移。EGF对滋养层细胞迁移具有剂量依赖性作用。低浓度的EGF（1 ng/ml）对细胞迁移具有刺激作用，而高浓度的EGF（100 ng/ml）显示出抑制作用。EGF（1 ng/ml）通过升高蛋白质水平和活性激活RhoA和RhoC，但不激活RhoB。EGF诱导的迁移被细胞渗透性C3外切酶转移酶或选择性RhoA或RhoC小干扰RNA抑制。抑制没有减轻通过添加EGF，这表明RhoA和RhoC在滋养层细胞迁移中发挥重要作用，是强制性的EGF行动。用RhoA小干扰RNA处理JEG-3和Tumor细胞诱导F-肌动蛋白细胞骨架破坏和细胞收缩，这与C3外切酶转移酶的作用一致，并且EGF处理不能减轻这种作用。RhoC小分子干扰RNA对F-actin重排无明显影响，提示RhoC通过F-actin重排参与EGF诱导的细胞迁移。这些结果表明，RhoA和RhoC发挥更重要的作用比RhoB EGF介导的滋养层细胞的迁移，和RhoA，而不是RhoC调节这种迁移通过F-肌动蛋白细胞骨架重组。（内分泌学151：1732-1742，2010）
This study investigated the roles of Rho protein in epidermal growth factor (EGF)-induced trophoblast cell migration and its mechanism. Using choriocarcinoma cell lines JEG-3 and JAR and first-trimester human chorionic villus explant cultures on matrigel, we examined EGF-mediated stimulation of trophoblast migration. EGF is shown to have a dose-dependent effect on trophoblast migration. A low concentration of EGF (1 ng/ml) has a stimulatory effect on cell migration, whereas high concentrations of EGF (100 ng/ml) shows an inhibitory effect. EGF (1 ng/ml) activates RhoA and RhoC, but not RhoB, through elevated protein levels and activity. EGF-induced migration was shown to be inhibited by either cell-permeable C3 exoenzyme transferase or selective RhoA or RhoC small interfering RNAs. The inhibition was not mitigated by the addition of EGF, suggesting that RhoA and RhoC play an important role in trophoblast migration and are obligatory for EGF action. Treatment of JEG-3 and JAR cells with RhoA small interfering RNA induced F-actin cytoskeleton disruption and cell shrinkage, which is consistent with the effect of C3 exoenzyme transferase, and this action was not mitigated by EGF treatment. RhoC small interfering RNA had no apparent effect on the F-actin arrangement, suggesting that RhoA but not RhoC takes part in the EGF induced migration through F-actin rearrangement. These results indicate that RhoA and RhoC play more important roles than RhoB in EGF-mediated migration of trophoblast cells, and RhoA but not RhoC regulates this migration through F-actin cytoskeleton reorganization. (Endocrinology 151: 1732-1742, 2010)